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Gaseous sulfur-containing compounds are the main products in tumours and preventing the diffusion of these compounds reduces the tumour proliferation rate, which suggests the possibility of a new approach to cancer treatment.

Background Betaine (glycine betaine or trimethylglycine) plays important roles as an osmolyte and a methyl donor in animals. While betaine is reported to suppress expression of proinflammatory molecules and reduce oxidative stress in aged rat kidney, the effects of betaine on the central nervous system are not well known. In this study, we investigated the effects of betaine on lipopolysaccharide (LPS)-induced memory impairment and on mRNA expression levels of proinflammatory molecules, glial markers, and GABA transporter 2 (GAT2), a betaine/GABA transporter. Methods Mice were continuously treated with betaine for 13 days starting 1 day before they were injected with LPS, or received subacute or acute administration of betaine shortly before or after LPS injection. Then, their memory function was evaluated using Y-maze and novel object recognition tests 7 and 10-12 days after LPS injection (30 μg/mouse, i.c.v.), respectively. In addition, mRNA expression levels in hippocampus were measured by real-time RT-PCR at different time points. Results Repeated administration of betaine (0.163 mmol/kg, s.c.) prevented LPS-induced memory impairment. GAT2 mRNA levels were significantly increased in hippocampus 24 hr after LPS injection, and administration of betaine blocked this increase. However, betaine did not affect LPS-induced increases in levels of mRNA related to inflammatory responses. Both subacute administration (1 hr before, and 1 and 24 hr after LPS injection) and acute administration (1 hr after LPS injection) of betaine also prevented LPS-induced memory impairment in the Y-maze test. Conclusions These data suggest that betaine has protective effects against LPS-induced memory impairment and that prevention of LPS-induced changes in GAT2 mRNA expression is crucial to this ameliorating effect.

To test the feasibility of using bacterial artificial chromosomes (BAC) containing kinases for pathological diagnosis using fluorescence in situ hybridization (FISH), 10 BAC probes containing a gene amplified in 5% or more of a pilot cohort were selected from a previous survey using arbitrarily selected BAC clones harboring 100 kinases. In this report, we describe the prevalence and association with the clinicopathological profile of these selected 10 BAC probes in 365 gastric cancer tissues. FISH analyses using these 10 BAC probes containing loci encoding EGFR, ERBB2(HER2), EPHB3, PIK3CA, MET, PTK7, ACK1, STK15, SRC, and HCK showed detectable amplifications in paraffin-embedded tissue in 2.83% to 13.6% of the gastric cancer tissues. Considerable numbers of the cases showed the co-amplification of two or more of the probes that were tested. BAC probes located within a genome neighborhood, such as PIK3CA, EPHB3, and ACK1 at 3q26-29 or HCK, SRC, and STK15 at 20q11-13.1, were often co-amplified in the same cases, but non-random co-amplifications of genes at distant genomic loci were also observed. These findings provide basic information regarding the creation of a strategy for personalizing gastric cancer therapy, especially when using multiple kinase inhibitors.

Objective: Transnasal endoscopy may be used to observe the head and neck part readily without excessive reflexes. We aimed to evaluate the utility and stability of transnasal esophagogastroduodenoscopy (TN-EGD) in comparison with transoral EGD (TO-EGD) for observation of the pharynx.Study Design: Prospective studyMethods: A total of 497 patients received unsedated TN-EGD with a 5.5 mm diameter endoscope or unsedated TO-EGD with endoscopes of 6.5 mm, 7.9 mm and 9.2 mm diameter. The rate of completion of pharyngeal observation and numbers of gag reflexes and cough reflexes were recorded.Results: TN-EGD was performed in 175 patients and TO-EGD was performed in 322 patients. Pharyngeal observation was completed in 173 patients (98.9%) in the TN-EGD group and 235 patients (73.2%) in the TO-EGD group, a significant difference (p<0.001). The TN-EGD group had a low rate of occurrence of gag reflex (0.57%), in contrast, 28.3% of the TO-EGD group had a gag reflex, a significant difference (p<0.01). Multivariable analyses revealed that the use of TN-EGD was the only predictive factor for completion of pharyngeal observation (p<0.0001).Conclusions: TN-EGD is ideally suited to observation of the pharynx by unsedated EGD.

We established adrenal medullary cell lines from transgenic mice expressing an oncogene, the temperature-sensitive simian virus 40 large T-antigen, under the control of the tyrosine hydroxylase promoter. A clonal cell line, named tsAM5D, conditionally grew at a permissive temperature of 33°C and exhibited the dopaminergic chromaffin cell phenotype as exemplified by the expression pattern of mRNA for catecholamine-synthesizing enzymes and secretory vesicleassociated proteins. tsAM5D cells proliferated at the permissive temperature in response to basic fibroblast growth factor (bFGF) and ciliary neurotrophic factor (CNTF). At a non-permissive temperature of 39°C, bFGF and CNTF acted synergistically to differentiate tsAM5D cells into neuron-like cells. In addition, tsAM5D cells caused to differentiate by bFGF plus CNTF at 39°C became dependent solely on nerve growth factor for their survival and showed markedly enhanced neurite outgrowth. In the presence of bFGF and CNTF, the morphological change induced by the temperature shift was associated with up-regulated expression of neuronal marker genes including neuron-specific enolase, growth-associated protein-43, microtubule-associated protein 2, neurofilament, and p75 neurotrophin receptor, indicating that the cells underwent neuronal differentiation. Thus, we demonstrated that tsAM5D cells could proliferate at permissive 33°C, and also had the capacity to terminally differentiate into neuronlike cells in response to bFGF and CNTF when the oncogene was inactivated by shifting the temperature to non-permissive 39°C. These results suggest that tsAM5D cells should be a good tool to allow a detailed study of mechanisms regulating neuronal differentiation. Keywords: adrenal chromaffin cells, immortalization, neuronal differentiation, neurotrophic factor, temperature-sensitive SV40 T-antigen, tsAM5D cells. Address correspondence and reprint requests to Norio Kaneda, Department of Analytical Neurobiology, Faculty of Pharmacy, Meijo University, Tempaku, Nagoya 468-8503, Japan. E-mail: nkaneda@ccmfs.meijo-u.ac.jp Abbreviations used 1: AADC, aromatic L-amino acid decarboxylase; BDNF, brain-derived neurotrophic factor; bFGF, basic fibroblast growth factor; CgA, chromogranin A; CgB, chromogranin B; ChAT, choline acetyltransferase; CNTF, ciliary neurotrophic factor; DBH, dopamine b-hydroxylase; DMEM, Dulbecco's modified Eagle medium; FBS, fetal bovine serum; GAP-43, growth-associated protein-43; GDNF, glia cell line-derived neurotrophic factor; MAP2, microtubule-associated protein 2; MTS tetrazolium, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium; NF160K, 160-kDa neurofilament; NF200K, 200-kDa neurofilament; NF68K, 68-kDa neurofilament; NGF, nerve growth factor; NSE, neuron-specific enolase; NT-3, neurotrophin-3; PNMT, phenylethanolamine N-methyltransferase; p75NTR, p75 neurotrophin receptor; SgII, secretogranin II; SV40T, simian virus 40 large T-antigen; TH, tyrosine hydroxylase; TrkA, tyrosine kinase A; tsSV40T, temperature-sens...

WE is superior to AI for attenuating insertion pain during colonoscopy without sedation, but its efficacy is limited in more painful endoscopy.

AIM:To investigate the usefulness of magnetic resonance cholangiopancreatography (MRCP) and the need for endoscopic retrograde cholangiopancreatography (ERCP) in cases of suspected spontaneous passage of stones into the common bile duct. METHODS:Thirty-six patients with gallbladder stones were clinically suspected of spontaneous passage of stones into the common bile duct because they presented with clinical symptoms such as abdominal pain and fever, and showed signs of inflammatory reaction and marked rise of hepatobiliary enzymes. These symptoms resolved and they showed normalized values of blood biochemical parameters after conservative treatment without evidence of stones in the common bile duct on MRCP. All these patients were subjected to ERCP within 3 d of MRCP to check for the presence of stones. RESULTS:No stones were detected by ERCP in any patient, confirming the results of MRCP. CONCLUSION:When clinical symptoms improve, blood biochemical parameters have normalized, and MRCP shows there are no stones in the common bile duct, it can be considered the stone has spontaneously passed and thus ERCP is not necessary.